Metabolism and Metabolic Regulation

Metabolism involved biological reactions and non-biological reactions which need organisms to lives life. Metabolism includes the conjugation, reduction, dehydroxylation, cyclization, methylation, phosphorylation, and oxidation of substrates (beta-oxidation of fatty acid, glucose, etc.) and the liberation of energy, heat, and carbon dioxide. Metabolism is considered as:

Primary metabolism: Primary metabolism is vital for keeps the functioning of the normal biological system. Metabolites in primary metabolism are highly specific throughout a wide variety of animals.

Secondary metabolism: Secondary metabolism is considered noncritical but advantageous to increase the tolerance and competence of organisms to external stimuli. Secondary metabolites are produced in the species-specific or organ-specific biosynthetic pathways.

• Metabolism is a highly coordinated cellular process in which uses many multi-enzyme systems.

• Obtain chemical energy by capturing sunlight energy or break down energy-rich molecules from the environment.

• Convert nutrients molecules into the cell’s own characteristics molecules include precursors of macromolecules.

• Polymerize monomeric precursors into macromolecules proteins, nucleic acids, and polysaccharides. (Anabolism)

• Synthesis and degrade biomolecules required for specialized cellular function such as membrane lipids, intracellular messengers, and pigments.

• The addition of all the chemical transformation taking place in cellular organisms founds through a series of enzymes catalyzed reactions that constitute metabolic pathway.

• The metabolic reaction depends on the rate enzyme. The enzyme can be increased and decrease the rate of reaction but not affect the reaction end products.

• Nicotine, caffeine, alcohol, dioxin, oranges, tangerines, and excess high amount of protein, hormones increase the rate of enzyme. These substances are already present in our bodies. Hypericum (bear) increases the rate of reaction cytochrome _p450. Flavonoids, furanocoumarins, naringenin, bergapten, and quercitin decrease the rate of reaction cytochrome _p450.

• Steps in a metabolic pathway bring about a specific small charge, usually the removal, transfer, or addition of a particular atom or functional group.

• Some metabolic pathway is linear and some are branched yielding multiple useful end products from a single precursor or converting several starting materials up to a signal product.

• The precursors are transformed into a product through a series of metabolic intermediates called metabolites.

• The intermediary metabolism is often applied to the combined activity of the entire metabolic pathway that interconverts precursor’s metabolites and products of low molecular weight.

Metabolism and Metabolic Regulation. Created with BioRender.com

Metabolism = Anabolism + Catabolism

Anabolism (Anabolic Pathway)

• The anabolic pathway is also called a biosynthesis pathway. In an Anabolic reaction, small and simple precursors are synthesis into larger and more complex molecules including lipids, polysaccharides, proteins, and nucleic acids.

• The anabolic pathway is divergent.

• The anabolic reaction requires an input of energy, generally in the form of the phosphoryl group transfer potential of ATP and the reading power of NADH, NADPH, and FADH_2.

Catabolism (Catabolic pathway)

• Catabolism is the process of the breakdown/degradative condition of metabolism in which organic nutrients molecules carbohydrates, lipids, and protein are transformed into small and simple end products. The major catabolic pathway is in which cells obtain energy from the oxidation of various fuels. Example:  Lactic acid, CO_2, and NH₃.

• The catabolic pathway is convergent.

• Catabolic reactions release energy, some of which is conserved in the synthesis of ATP and release electron carriers (NADH, NADPH, and FADH₂), the rest of lost as heat.

Metabolism Regulation

• Metabolic cycles are regulated at many steps, from within the cell and from outside. The most immediate regulation is by the availability of substrate, when the intracellular concentration of an enzyme-substrate is near/below Km, the rate of the reaction depends strongly on substrate concentration.

• The second type of control from within is allosteric regulation by a metabolic intermediate coenzyme an amino acid or ATP.

• In some cases, this regulation founds virtually instantaneously through alters in the levels of intracellular messengers that modify the activity of existing enzyme molecules by allosteric mechanisms or by covalent modification such as phosphorylation.

• In other cases, the extracellular signal changes the cellular concentration of the enzyme by changing the rate of its synthesis or degradation. So that effect is seen only after minutes or hours.

Cancer Metabolism

Energy metabolism can very important among cancer patients. In cancer cells show uncontrolled manner growth. Metabolism is reprogrammed in cancer to increase the anabolism of cellular building blocks, generation of ATP and energy uses the maintain rapid cell growth. In cancer cells, aerobic glycolysis changes glucose to lactate while increasing glucose transport through the HMP (Hexose monophosphate pathway)/Phosphogluconate pathway/ PPP and serine /glycine pathway. HMP pathway is an alternative pathway for glucose oxidation. Glutamine is also used to fuel the Krebs cycle (TCA) which provides intermediates for anabolic pathways such as nucleotide metabolism, leaving many cancer cells glutamine dependent. Cancerous cells promote de novo lipogenesis to provide sufficient amounts of lipids for energy storage and membrane synthesis. In cancer metabolism hypoxia, overexpression of MYC, loss of p⁵³, mutation of KRAS, and constitutive PI3K/AKT and mTOR activation is known to play important roles.